TMEM70 mutations cause isolated ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy.
We carried out whole-genome homozygosity mapping, gene expression analysis and DNA sequencing in individuals with isolated mitochondrial ATP synthase deficiency and identified disease-causing mutations in TMEM70. Complementation of the cell lines of these individuals with wild-type TMEM70 restored biogenesis and metabolic function of the enzyme complex. Our results show that TMEM70 is involved in mitochondrial ATP synthase biogenesis in higher eukaryotes.
Cízková
Alena
A
Institute of Inherited Metabolic Disorders, Charles University of Prague, First Faculty of Medicine, Prague 12808, Czech Republic.
Stránecký
Viktor
V
Mayr
Johannes A
JA
Tesarová
Markéta
M
Havlícková
Vendula
V
Paul
Jan
J
Ivánek
Robert
R
Kuss
Andreas W
AW
Hansíková
Hana
H
Kaplanová
Vilma
V
Vrbacký
Marek
M
Hartmannová
Hana
H
Nosková
Lenka
L
Honzík
Tomás
T
Drahota
Zdenek
Z
Magner
Martin
M
Hejzlarová
Katerina
K
Sperl
Wolfgang
W
Zeman
Jirí
J
Houstek
Josef
J
Kmoch
Stanislav
S
D009202:Cardiomyopathies / Q000150:complications / Q000201:enzymology* / Q000235:genetics*; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005816:Genetic Complementation Test; D006801:Humans; D007231:Infant, Newborn; D008565:Membrane Proteins / Q000235:genetics*; D017237:Mitochondrial Encephalomyopathies / Q000150:complications / Q000201:enzymology* / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D025261:Mitochondrial Proton-Translocating ATPases / Q000172:deficiency*; D009154:Mutation / Q000235:genetics*; D014162:Transfection
D018076:DNA, Complementary; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C533106:TMEM70 protein, human; D025261:Mitochondrial Proton-Translocating ATPases